title: Design and synthesis of a novel cationic thiolated polymer.
abstract: The purpose of this study was to design and characterize a novel cationic thiolated polymer. In this regard a hydroxyethylcellulose-cysteamine conjugate (HEC-cysteamine) was synthesized. Oxidative ring opening with periodate and reductive amination with cysteamine were performed in order to immobilize free thiol groups to HEC. The resulting HEC-cysteamine displayed 2035 ± 162 μmol immobilized free thiol groups and 185 ± 64 μmol disulfide bonds per gram of polymer being soluble in both acidic and basic conditions. Unlike the unmodified HEC, in case of HEC-cysteamine, a three-fold increase in the viscosity was observed when equal volumes of the polymer were mixed with mucin solution. Tablets based on HEC-cysteamine remained attached on freshly excised porcine mucosa for 8 0h and displayed increased disintegration time of 2h. Swelling behavior of HEC-cysteamine tablets in 0.1M phosphate buffer pH 6.8 indicated swelling ratio of 19 within 8h. In contrast, tablets comprising unmodified HEC detached from the mucosa within few seconds and immediately disintegrated. In addition, they did not exhibit swelling behavior. The transport of rhodamine 123 across freshly excised rat intestine enhanced by a value of approximately 1.6-fold (p-value = 0.0024) in the presence of 0.5% (m/v) HEC-cysteamine as compared to buffer control. Result from cytotoxicity test of HEC-cysteamine applied to Caco-2 cells in concentration of 0.5% (m/v) revealed 82.4 ± 4.60% cell viability. According to these results, HEC-cysteamine seems to be a promising polymer for various pharmaceutical applications especially for intestinal drug delivery.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 52, Josef Möller Haus, 6020 Innsbruck, Austria.
authors.forename: Deni
authors.initials: D
authors.lastname: Rahmat
authors.forename: Duangkamon
authors.initials: D
authors.lastname: Sakloetsakun
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.forename: Glen
authors.initials: G
authors.lastname: Perera
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kaindl
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000269:Adhesives / Q000032:analysis / Q000138:chemical synthesis; D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry; D002412:Cations / Q000032:analysis / Q000138:chemical synthesis; D002482:Cellulose / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis; D003543:Cysteamine / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007413:Intestinal Mucosa / Q000378:metabolism; D010539:Permeability; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D020112:Rhodamine 123 / Q000378:metabolism; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013607:Tablets
chemical_list: D000269:Adhesives; D000447:Aldehydes; D002412:Cations; D004337:Drug Carriers; D011108:Polymers; D013438:Sulfhydryl Compounds; D013607:Tablets; D020112:Rhodamine 123; D003543:Cysteamine; D002482:Cellulose; C002283:hydroxyethylcellulose